title: Calorie restriction in overweight males ameliorates obesity-related metabolic alterations and cellular adaptations through anti-aging effects, possibly including AMPK and SIRT1 activation.
abstract: BACKGROUND
  Calorie restriction (CR) is accepted as an experimental anti-aging paradigm. Several important signal transduction pathways including AMPK and SIRT1 are implicated in the regulation of physiological processes of CR. However, the mechanisms responsible for adaptations remain unclear in humans.
  
  
  METHODS
  Four overweight male participants were enrolled and treated with 25% CR of their baseline energy requirements for 7weeks. Characteristics, including body weight (BW), body mass index (BMI), %fat, visceral fat area (VFA), mean blood pressure (MBP) and VO2 max, as well as metabolic parameters, such as insulin, lipid profiles and inflammatory makers and the expression of phosphorylated AMPK and SIRT1 in peripheral blood mononuclear cells (PBMNCs), were determined at baseline and then after 7weeks. In addition, we assessed the effects of the serum collected from the participants on AMPK and SIRT1 activation and mitochondrial biogenesis in cultured human skeletal muscle cells.
  
  
  CONCLUSIONS
  After CR, BW, BMI, %fat, VFA and MBP all significantly decreased, while VO2 max increased, compared to those at baseline. The levels of fasting insulin, free fatty acid, and inflammatory makers, such as interleukin-6 and visfatin, were significantly reduced, whereas the expression of phosphorylated AMPK and SIRT1 was significantly increased in PBMNCs collected after CR, compared to those at baseline. The skeletal muscle cells that were cultured in serum collected after CR showed an increase in AMPK and SIRT1 activity as well as mitochondrial biogenesis.
  
  
  CONCLUSIONS
  CR is beneficial for obesity-related metabolic alterations and induces cellular adaptations against aging, possibly through AMPK and SIRT1 activation via circulating factors.
authors.affiliation: Diabetology and Endocrinology, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
authors.forename: Munehiro
authors.initials: M
authors.lastname: Kitada
authors.forename: Shinji
authors.initials: S
authors.lastname: Kume
authors.forename: Ai
authors.initials: A
authors.lastname: Takeda-Watanabe
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Tsuda
authors.forename: Keizo
authors.initials: K
authors.lastname: Kanasaki
authors.forename: Daisuke
authors.initials: D
authors.lastname: Koya
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism*; D000328:Adult; D031204:Caloric Restriction; D002478:Cells, Cultured; D004789:Enzyme Activation; D006801:Humans; D008297:Male; D008659:Metabolic Diseases / Q000150:complications* / Q000201:enzymology / Q000378:metabolism; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism; D009765:Obesity / Q000150:complications* / Q000201:enzymology / Q000378:metabolism; D050177:Overweight / Q000178:diet therapy*; D060888:Real-Time Polymerase Chain Reaction; D056564:Sirtuin 1 / Q000378:metabolism*
chemical_list: D000263:Adenylate Kinase; C447939:SIRT1 protein, human; D056564:Sirtuin 1
keywords: AMPK; Calorie restriction; Mitochondrial biogenesis; SIRT1